Method and system for aseptically filling a package

ABSTRACT

The present invention relates to a method and system for aseptically filling of flexible packages containing dry cloth. Such a method may include a first stage that is performed in a non-sterile environment. The first stage may include cutting a first substantially dry cloth to a predetermined size; inserting the first cloth into a flexible package; sealing a first end of the flexible package; and sterilizing the flexible package. The method may also include a second stage performed in a sterile environment. The second stage may include filling the flexible package with a medical solution such that the substantially dry cloth absorbs at least a portion of the medical solution; and sealing the an open end of the flexible package.

BACKGROUND

Some embodiments relate generally to aseptically filling a package andmore particularly to aseptically filling a package containing a clothwith a medical solution for use in healthcare.

The healthcare and other industries use aseptic and/or sterile products,for example, cloths to clean wounds and prepare a patient for surgery.Such cloths can be at least partially saturated with a medical solution,for example, an alcohol solution. Another medical solution that may beused is Chlorhexidine gluconate (“CHG”).

CHG is a chemical antiseptic that is currently approved and marketed forboth inpatient and outpatient use in skin cleansing products, oralrinses, and in pre-surgical applications. Chlorhexidine gluconate is apotent membrane-active anti-bacterial agent with activity against abroad range of Gram-positive and Gram-negative bacteria. At lowconcentrations, CHG is bacteriostatic, disrupting cell membranefunction. At higher concentrations, CHG is bactericidal against a widerange of bacteria and yeast, irreversibly disrupting cell membraneintegrity and leading to intracellular leakage.

The chemical name of CHG is 2,4,11,13-Tetraazatetradecanedimidamide,N,N″-bis(4-chlorophenyl)-3,12-diimino-, di-D-gluconate. The empiricalformula of CHG is C₂₂H₃₀Cl₂N₁₀.2C₆H₁₂O₇ and its molecular weight is897.76.

Chlorhexidine gluconate was first approved by the Topical AntimicrobialsCommittee of the FDA in 1976 as a surgical hand scrub under thetradename Hibiclens®. Since then, multiple other CHG products have alsobeen approved by the FDA for various antiseptic indications. Inhospitals, CHG is commonly used for surgical site preparation and as askin cleanser to reduce the number of microorganisms on the skin.

Current methods of sterilizing healthcare products, however, are eitherunsuitable for the contents of a package using CHG or other medicalsolutions, or may degrade one or more qualities of the medical solution.

Thus, there is a need for a method of aseptically filling a package formedical use.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an schematic illustration of a system for filling a packageaccording to an embodiment;

FIG. 2 is an illustration of a package according to an embodiment;

FIG. 3 is an illustration of a package according to a second embodiment;

FIG. 4 is an illustration of a first portion of a room according to anembodiment;

FIG. 5 is an illustration of a second portion of the room shown in FIG.3;

FIG. 6 is an illustration of a third portion of the room shown in FIG.3;

FIG. 7 is a flowchart showing a method of filling a package according toan embodiment.

FIG. 8 is a flowchart showing a method of filling a package according toan embodiment.

DETAILED DESCRIPTION

In describing the embodiments of the invention in detail and referringto the drawings, like numbers indicate like parts throughout thefigures. As used in the description herein and throughout the claims,the following terms take the meanings explicitly associated herein,unless the context clearly dictates otherwise: the meaning of “a,” “an,”and “the” includes plural reference, the meaning of “in” includes “in”and “on.” Relational terms such as first and second, top and bottom, andthe like may be used solely to distinguish one entity or action fromanother entity or action without necessarily requiring or implying anyactual such relationship or order between such entities or actions.

As used in this specification the term sterile can mean a sterileenvironment, process and/or product in that is free from contaminants inaccordance with a government and/or organizational regulation to a firstlevel of assurance. In some embodiments, the first level of assurancecan be 10-6. Similarly, the term aseptic can mean an sterileenvironment, process and/or product in that is free from contaminants inaccordance with a government and/or organizational regulation to asecond level of assurance, less stringent than the first level ofassurance. In some embodiments, the first level of assurance can be10-3. As used in this specification, the term sterile can include bothsterile and aseptic unless specifically noted.

As shown schematically in FIG. 1, a system 100 can be used to prepare apackage containing a cloth and a medical solution for shipping.Specifically, system 100 can be used to dispose a dry cloth into thepackage, sterilize the package containing the cloth, aseptically fillthe package with a medical solution, and seal the package for furtherpacking and/or shipping. The system 100 can include various modules forperforming associated steps of a packaging process. For example system100 may include a packing module 102, an insertion module 104, asterilization module 106, a removal module 108, a cutting module 112, afilling module 114 and a sealing module 116. In some embodiments, system100 can include a mechanized component to move a package from one moduleto another module for example, a conveyor module (not shown).

In some embodiments, each of the components of system 100 can bedisposed in a room, such as, for example, a clean room in accordancewith a clean room classification, such as, for example, an ISO cleanroom standard. In some embodiments, the components of system 100 can bedistributed over more than one room. In such embodiments, a first roomcan be in a first location, and a second room can be in a secondlocation, different from the first location, and the first location andsecond location can be separated by an intermediate location that maynot be in accordance with a clean room standard and/or may be adifferent clean room standard than the first room and/or the secondroom. In further embodiments, some steps of a process performed bysystem 100 may be conducted in a non-sterile environment, while othersteps are conducted in sterile environments with varying levels ofsterility assurance in order to achieve a finished product, including apackaged cloth with medical solution, having a certain level ofsterility. In one embodiment, the finished product has been renderedsterile to a sterility assurance of at least 10⁻³. In a furtherembodiment, the finished product has been rendered sterile to asterility assurance of at least 10⁻⁶. In another embodiment, a firstportion of the finished product can have been rendered sterile to afirst sterility assurance, for example, at least 10-3, and a secondportion can have been rendered sterile to a second sterility assurance,for example, at least 10-6.

As described above, system 100 can be used to pack and/or fill packages.In an embodiment, the package may be a flexible package as illustratedin FIG. 3. Such a package may be constructed from a flexible film. Forexample, the package material may be 0.48 mil PET/0.48 mil PET/2.25 milHDPE COEX film. In some embodiments, the package may be constructed of adifferent flexible film and/or can have different level of flexibility.In such an embodiment, the package can be substantially rigid, forexample, a plastic tub. The package is constructed by folding a sheet offilm into a generally tubular configuration and sealing the two abuttingends of the film together along seam 338. The package may then be sealedby applying appropriate sealing temperatures and parameters to createsealed ends 332 and 336. The step of sealing the ends 332,336 may occurat different stages of the process as described below.

Returning to FIG. 1, packing module 102 can insert a cloth into thepackage. In some embodiment packing module 102 can be configured toreceive the cloth having been previously cut to size and shape. In otherembodiments, packing module 102 can include a cutting component (notshown) that can be configured to receive cloth, for example, a bundle orroll of cloth, and can be configured to cut the cloth to a predeterminedsize and/or shape prior to packing the cloth in the package. In someembodiments, the cloth can be folded prior to packing in the package. Insome embodiments, packing module 102 can pack a plurality of cloths intothe package. In such embodiments, the plurality of cloths can bestacked, folded, or the like.

In an embodiment, each package will include two 8 inch by 8 inch cloths.Suitable cloths may include polyester, rayon, other natural and/orartificial fibers and/or blends. Additionally suitable cloths caninclude different size fibers. In some embodiments, a cloth can be anyshape and/or size. In some embodiments, a cloth can be similar to thecloths described in U.S. Pat. No. 7,427,574 entitled “Non-Woven WashCloth,” U.S. Pat. No. 7,066,916 entitled “Disinfectant Delivery System,and Method of Providing Alcohol-Free Disinfection,” and/or U.S. Pat. No.7,595,021 entitled “Method of Providing Alcohol-Free Disinfection, eachof which is herein incorporated by reference in their entirety.

Manufacturing of cloth related products includes a variety of challengesto maintaining a clean room environment. For example, slitting/cuttingof the cloth material creates dust and loose fibers that increase thedifficulty in maintaining the sterility of a manufacturing environment.In addition, there may be difficulties with effectively sterilizinglarge and/or dense rolls of cloth material. Accordingly, in embodimentsof the present invention, steps of the process performed in thepackaging module, including preparing the cloths and inserting them intothe package, may be performed in a non-sterile environment.

In some embodiments, system 100 can include a package sealing module(not shown), similar to sealing module 116 described herein, configuredto seal the package after packing module 102 inserts the cloth into thepackage. For example, as shown in FIG. 2, the package 220 can include afirst sealed end 222. The second end 224 may be left open for sealing ata later step in the process. Alternatively, as shown in FIG. 3, apackage 330 can include a first sealed end 332 and a second sealed end336.

Returning to FIG. 1, insertion module 104 can insert the package into awrap (not shown), for example, a plastic sheet or film that surroundsthe package, such as a polyethylene bag or other appropriate material.Said another way, the insertion module 104 can at least partially wrapthe package in the film wrap. The wrap can at least partially enclosethe package and can protect the package during transportation throughsystem 100 and/or can ensure the sterile environment is maintained bythe package after the package is sterilized. In some embodiments,insertion module 104 can insert a plurality of packages into a singlewrap. In some embodiments, the wrap is sealed. In such embodiments,insertion module 104 can include a component configured to seal thewrap. In other such embodiments, system 100 can includes a wrap sealingmodule (not shown), similar to sealing module 116 described herein,configured to seal the wrap. In some embodiments, insertion module 104can insert the package into two layers of wrap, or a wrap having atwo-layer wall.

Sterilization module 106 can sterilize the package, and/or the packageat least partially wrapped in wrap. In some embodiments, sterilizationmodule 106 can irradiate the package. In such embodiments, sterilizationmodule can expose the package to gamma radiation, for example, betweenabout 25 kGy and about 50 kGy. In some embodiments, other sterilizationmethods can be used, for example, heat, ethylene oxide, and/orcombinations of sterilization methods. As explained above, the presentinvention contemplates performing certain steps in a non-sterileenvironment. However, in order to preserve the sterility of the finishedproduct, embodiments of the invention contemplate that the removalmodule 108, cutting module 112, filling module 114 and sealing module116 will be located in one or more sterile environments.

Removal module 108 can remove the package from the wrap. In someembodiments, such as an embodiment where the wrap was sealed around thepackage, the removal module can be configured to cut and/or otherwiseopen the wrap. In some embodiments, system 100 can include a wrapcutting module (not shown) configured to cut and/or otherwise open thewrap.

In embodiments where the package includes a first sealed edge and asecond sealed edge (see, e.g., FIG. 3), cutting module 112 can cutand/or otherwise open the package. In some embodiments, cutting module112 can substantially remove the second sealed edge. In otherembodiments, cutting module 112 can pierce the package and/or otherwisedefine an aperture in the package.

Filling module 114 can be configured to aseptically fill the packagewith a medical solution (not shown). Filling module 114 can include afilter (not shown) configured to filter the medical solution. The filtercan be, for example, about a 0.2 μm/0.2 μm filter. In some embodiments,filling module 114 can include more than one filter. In suchembodiments, the more than one filter can be arranged in series and/orparallel. Filling module 114 can include a nozzle (not shown) configuredto direct a flow of medical solution into the package. In someembodiments, filling module 114 can include and/or can be configured tobe coupled to at least one storage location for storing medical solutionbefore and/or after filtering.

In some embodiments, the medical solution can include chlorhexidinegluconate (hereinafter “CHG”) solution and/or can include alcohol. Inone such embodiment, the medical solution can include about 2%-4% CHGprior to filtering. In another such embodiment, the medical solution caninclude at least about 50% alcohol. In such embodiments, the medicalsolution can include about 70% alcohol. In another such embodiment, themedical solution can include about 2% CHG and at least about 50%alcohol. In some embodiments, other antimicrobial and/or antisepticsolutions can be used, for example, povidone iodine, para chloro metaxylenol, benzalkonium chloride, ethyl alcohol, etc. In some embodimentsthe medical solution can includes surfactants and/or other skintreatment/care compounds and/or solutions, preservatives, processingingredients, inactive ingredients, etc.

Sealing module 116 can reseal the open end of the package, if the secondsealed edge of the package was removed, and/or can seal the open end ofthe package, if the open end of the package was not previously sealed.Sealing module 116 can be configured to seal the package at apredetermined temperature and/or pressure, and can be configured to sealthe package such that an area within the package is at a predeterminedpressure. In some embodiments, sealing module 116 can be an impulse heatsealer.

In some embodiments, the system 100 can include a stacking module (notshown) to stack, package and/or otherwise prepare the package forshipping and/or transportation to another room and/or destination.

FIGS. 4-6 depict portions of a room according to an embodiment that caninclude all or a portion of a system 400. System 400 can be similar tosystem 100 and can include similar components with similarcharacteristics. As shown in FIG. 4, system 400 can include a conveyorbelt 418 configured to move packages 420 (including a sealed end) and/orpackages 430 (including an open end) through system 400. System 400 caninclude a cutting module 412 that can include a vacuum system 442configured to pull a closed end 436 of a package 420 into a knifeassembly 444. Vacuum system 442 can include a vacuum pump 462 configuredto exert a negative pressure on the package such that knife assembly 444can cut, pierce or otherwise define an opening in package 420.

As shown in FIG. 5, system 400 can include a filling module 414. Thefilling module can include a dosing head and nozzle assembly 452 thatincludes at least one filter 454, and that is configured to direct aflow of a medical solution from a storage location 456 and into thepackage 420. Filling module 414 can include vacuum system 460 configuredto hold open an open end and/or other opening of package 420 during thefilling process. Vacuum system 460 can include a vacuum pump 462configured to exert a negative pressure on the one or more portions ofpackage 420. As shown in FIG. 6, system 400 can include a sealing module416. Sealing module 416 can include a sealing bar 472 configured to sealan open end 424 of package 420.

By way of example, with reference to FIG. 4-6, two 8″×8″ dry non-wovencloths, e.g. substantially free of medical solution and or othernon-ambient moisture, can be disposed within a flexible package by apackaging module in a first room. The flex package can be sealed and thepackage can include a first sealed edge and a second sealed edge. Theflexible package can be inserted into a polyethylene bag (film). Thepolyethylene bag containing the package can be placed in a containerapproved for use in a clean room and configured to not impedesterilization. The container including the polyethylene bag and packagecan then be transported to a second room and sterilized via exposure togamma radiation between about 25 kGy and about 50 kGy.

Continuing with the example, a medical solution can be prepared thatincludes 2%-4% CHG. The medical solution can be disposed in a storagelocation 456 and coupled to nozzle assembly 452 of filling module 414which can be disposed in a third room that can be a clean room. Thecontainer can be transported to the third room, and can be prepared forentrance into the third room in accordance with a predetermined cleanroom standard. Removal module can remove the package from thepolyethylene bag, package holder 410 and conveyor belt 418 can transportthe package to cutting module 412. Vacuum system 442 of cutting module412 can exert a negative pressure on the package and can pull the secondsealed edge of the package into the knife assembly 444 of cutting module412. Knife assembly 444 can remove the second edge 224 and/or otherwisedefine an opening in the package.

Continuing with the example, conveyor belt 418 can transport the packageto filling module 414. The vacuum system 460 of filling module 414 canexert a negative pressure on at least one portion of the package suchthat the opening in the package is held open. Nozzle assembly 452 candispense a predetermined amount of medical solution, for example, about70 ml, from the storage location 456, through the filters 454 and intothe package. Conveyor belt 418 can transport the package to the sealingmodule 416. The opening of the package can be positioned adjacent thesealing bar 472 of sealing module 416 and sealed. Conveyor belt 418 canthen transport the package to a hopper or other module for furtherpackaging.

While it is contemplated in some embodiments that the components ofsystem 400 are located in a single sterile environment, the presentinvention also encompasses systems and methods in which the varioussteps described are located in separate rooms or environments. In suchembodiments, the incomplete products may be moved from one environmentto another in any appropriately sterile manner.

FIG. 7 is a flowchart depicting a method 700 of aseptically filling apackage. The method 700 can includes a first stage and a second stage.The first stage of method 700 can be performed in a non-sterileenvironment and can include cutting a first substantially dry cloth to apredetermined size, at 702. The first stage can include inserting thefirst cloth into a flexible package, at 704. The first stage can includesealing a first end of the flexible package, at 706. The first stage caninclude sterilizing the flexible package, at 708. The second stage ofmethod 700 can be performed in a sterile environment and can includefilling the flexible package with a medical solution such that thesubstantially dry cloth absorbs at least a portion of the medicalsolution, at 710. The second stage can include sealing an open end ofthe flexible package, at 712.

FIG. 8 is a flowchart depicting a method 800 of aseptically filling apackage. Method 800 includes disposing a package that includes asubstantially dry cloth within a film wrap to define a wrapped package,at 802. Method 800 includes irradiating the wrapped package, at 804.Method 800 includes removing the package from the wrap, at 806. Method800 includes filling, from an outlet downstream of an aseptic filter,the package with a medical solution such that the substantially drycloth absorbs at least a portion of the medical solution, at 808. Method800 includes sealing the package, at 810.

An embodiment of the present invention comprises the steps of: (1)package two 8 inch by 8 inch cloths dry (without solution or moisture)in flexible film container at using appropriate sealing temperatures andparameters for 0.48 mil PET/0.48 mil PET/2.25 mil HDPE COEX film; (2)after sealing, secure packages in two layers of polyethylene bags andplace in clean room and radiation appropriate outer container; (3)sterilize packages using a range from 25-50 kGy; (4) prepare 2% CHGsolution containing glucono-delta-lactone and fill into pre-sterilizedcontainer for transfer into aseptic environment; (5) prepare sterilefiltering apparatus by appropriate cleaning including pump, tubing,stands, sealer etc for transfer into aseptic environment; (6) preparepost irradiated packages by appropriate cleaning for entry into Class100 laminar flow environment for aseptic filling; (7) remove packagesfrom inner polyethylene bag and transfer into the Class 100 area; (8)cut one end of the package with pre-sterilized surgical scissors; (9)using pre-programmed pump settings fill packages with 2% CHG Solutionusing 0.2 μm/0.2 μm sterile filter and peristaltic pump to a target fillvolume of 70 ml; (10) reseal the open end using a sealer at pre-definedtemperature and pressure settings; (11) remove sterile filled packagesfrom Class 100 environment.

In an alternative embodiment, hard packages made of polyethylene orother appropriate material may be used. Such hard packages may comprisetubs using separate or flip-top lids. If such a hard package is used,the packages will be puctured, aseptically filled with solution, andsealed. Alternatively, the process could include shrink wrapping a tubwithout the lid, sterilizing the tubs and lids separately, removing theshrink wrap, aseptically filling the tubs, sealing and placing the lidson the tubs, and shrink wrapping the tubs and lids.

While various embodiments have been described above, it should beunderstood that they have been presented by way of example only, and notlimitation. Where methods described above indicate certain eventsoccurring in certain order, the ordering of certain events can bemodified. Additionally, certain of the events can be performedconcurrently in a parallel process when possible, as well as performedsequentially as described above. Although various embodiments have beendescribed as having particular features and/or combinations ofcomponents, other embodiments are possible having a combination of anyfeatures and/or components from any of embodiments where appropriate.Furthermore, while certain temperatures, pressures, and othermeasurements, calculations, and/or other values are described inapproximate terms, the values used are not meant to be exact and a rangeof values can be used, for example plus or minus 10 percent.

While the present disclosure and what the best modes of the inventionshave been described in a manner establishing possession hereof by theinventors and enabling those of ordinary skill in the art to make anduse the same, it will be understood and appreciated that there are manyequivalents to the exemplary embodiments disclosed herein and thatmodifications and variations may be made thereto without departing fromthe scope and spirit of the inventions, which are to be limited not bythe exemplary embodiments but by the appended claims.

What is claimed:
 1. A method, comprising: a first stage of the methodperformed in a first environment, the first environment beingnon-sterile, the first stage comprising the steps of: first cutting asubstantially dry cloth to a predetermined size; second inserting thesubstantially dry cloth into a substantially tubular flexible package;third sealing a first end of the flexible package; and fourthsterilizing the flexible package by irradiating the flexible package; asecond stage of the method performed in a second environment, the secondenvironment being sterile, the second stage comprising the steps of:first filling the flexible package with a medical solution such that thesubstantially dry cloth absorbs at least a portion of the medicalsolution; and second sealing a second end of the flexible package. 2.The method of claim 1, wherein sterilizing the flexible package includesexposing the flexible package to between 25 kGy and 50 kGy.
 3. Themethod of claim 1, the first stage further comprising sealing the secondend of the flexible package after sealing the first end of the packageand the second stage further comprising opening the second end of theflexible package prior to filling the flexible package.
 4. The method ofclaim 3, wherein opening the second end of the flexible packagecomprises cutting a sealed portion from the second end of the flexiblepackage.
 5. The method of claim 1, wherein the first stage furthercomprises at least partially enclosing the flexible package in a wrap.6. The method of claim 5, wherein the flexible package is fully enclosedin the wrap.
 7. The method of claim 6, wherein the wrap comprises apolyethylene bag.
 8. The method of claim 1, wherein filling the flexiblepackage with the medical solution includes aseptically filling theflexible package with the medical solution.
 9. The method of claim 1,wherein the medical solution includes chlorhexidine gluconate.
 10. Themethod of claim 1, wherein the medical solution includes about 2%chlorhexidine gluconate.